We are conducting a series of clinical investigations in patients with systemic lupus erythematosus to address questions related to disease pathogenesis, epidemiology, therapy and co-morbidities. A large cohort of patients with lupus nephritis has been assembled over the past several decades who have participated in long-term, randomized trials of corticosteroids and immunosuppressive drugs. These studies have documented the important role of intravenous cyclophosphamide in the preservation of renal function in patients with severe, proliferative lupus glomerulonephritis . Extended follow-up of these patients is ongoing to ascertain rates of relapse of the nephritis and late complications of immune suppression. We are also interested in conducting phase I/II clinical trials of promising therapies in patients with lupus nephritis. During the past year we have completed studies of the nucleoside analog 2-chloro-2'deoxyadenosine and recombinant human DNase. Studies are underway to assess risk factors associated with the development of osteoporosis and vascular thrombotic events.